Cardiotoxicity is one of the major forms of toxicity seen in drugs and it accounts for most recalls and delays experienced in drug approvals.

One of the biggest challenges is how to predict cardiac risk associated with drug candidates very early and accurately in the drug development process.

This short course is designed to get researchers and clinicians to question the predictive validity of current cardiac risk assessment strategies and to get them thinking about ways to improve preclinical predictors of cardiac safety.

The course will provide an overview of the recent technical and scientific advances in preclinical safety testing such as, improvements in assay design and reagents, availability of new cell lines for in vitro toxicity screening, use of toxicogenomics and other tools for developing safety biomarkers and the success of in silico predictive models for determining cardiac safety.

The instructors will also talk about ways to then effectively combine the intelligence gathered from preclinical screens with clinical data and post-marketing pharmacovigilance studies from other drugs, to better assess risk to benefit ratios for new drug candidates.

In this short course, the faculty will highlight the number of industries that depend on cell culture and include how each can benefit from the 3D paradigm. For example, high-throughput screening and cell-based assay groups will be able to test compounds within more relevant cells.

Public health officials and biomanufacturers will be able to respond more rapidly and regionally prior to potential pandemics. Furthermore, the discovery and production of humanized biotech drugs will benefit from a standard and scalable 3D cell culture process.

New media formulations will provide the added nutritional support and buffering required for high production cell culture systems. Media design for small scale and manufacturing processes will also be featured.

This course will cover novel approaches to performing metabolite identification in drug metabolism, structure toxicity relationships and how useful they are in predicting toxicities of new drugs. This portion of the course will also demonstrate how to improve the decision-making process in structural modification of drug candidates and reduce toxicity and improve metabolic stability and PK.

This portion of the course will cover the role of cytochrome P450 enzymes in drug-drug interactions in addition to illustrating how toxicity screening using biosensors that measure DNA damage can be useful. Strategies to assess the drug interactions and future FDA guidelines will be addressed.

Animal models have led to countless healthy mice but too often fall short when a drug is tested in human subjects. Microdosing studies offer an alternative to animal models with the ‘first in man’ approach of administering 1% of a pharmacological dose at Phase 0. Coupled with ultra-sensitive detection technology (Accelerator Mass Spectrometry, PET, LC/MS/MS), microdosing can determine a compound’s PK and bioavailability, and failures can be identified much earlier in the development process before reaching expensive clinical trials. Experts who have performed microdosing studies will give indepth presentations to define microdosing and illustrate how it works including case studies. The goal of this workshop is to provide you with up-to-date and helpful information about this innovation for identifying the most promising candidates -- because the mouse is not a good human.

Tutors:
Ali Arjomand, Ph.D., President & COO, Accium BioSciences Inc
Punam Sandhu, Ph.D., Research Fellow, Department of Drug Metabolism, Merck & Co.
Lloyd Stevens, Ph.D., Principal Scientist, Pharmaceutical Profiles Ltd.

This short course will highlight specific steps to building better animal models for drug development in the pain area. The session will begin by addressing the ethical considerations of animal research and a framework for identifying appropriate species and models (e.g. surgical v. irritant, disease specific v. general). You will also learn how to better identify and understand the critical biological, histological and electrophysiological endpoints of your programs. Special attention to the applications of animal research in inflammatory, neuropathic and cancer pain will be given during this session.

Tutor: Daniele Carettoni, Ph.D., Head, Biochemistry, Axxam SpA
Xuedong Liu, Ph.D., Associate Professor, Department of Chemistry and Biochemistry, University of Colorado-Boulder